Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2020 Feb 18;10(2):323.
doi: 10.3390/biom10020323.

Hydrogen Sulfide in Pharmacotherapy, Beyond the Hydrogen Sulfide-Donors

Ewelina Zaorska  1 , Lenka Tomasova  2 , Dominik Koszelewski  3 , Ryszard Ostaszewski  3 , Marcin Ufnal  1
Affiliations
Review

Hydrogen Sulfide in Pharmacotherapy, Beyond the Hydrogen Sulfide-Donors

Ewelina Zaorska et al. Biomolecules. .

Abstract

Hydrogen sulfide (H2S) is one of the important biological mediators involved in physiological and pathological processes in mammals. Recently developed H2S donors show promising effects against several pathological processes in preclinical and early clinical studies. For example, H2S donors have been found to be effective in the prevention of gastrointestinal ulcers during anti-inflammatory treatment. Notably, there are well-established medicines used for the treatment of a variety of diseases, whose chemical structure contains sulfur moieties and may release H2S. Hence, the therapeutic effect of these drugs may be partly the result of the release of H2S occurring during drug metabolism and/or the effect of these drugs on the production of endogenous hydrogen sulfide. In this work, we review data regarding sulfur drugs commonly used in clinical practice that can support the hypothesis about H2S-dependent pharmacotherapeutic effects of these drugs.

Keywords: H2S donors; H2S pro-drugs; anti-inflammatory agents; anticancer drug; cardiovascular; hydrogen sulfide; neuromodulation; sulfur-containing drugs.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Examples of hydrogen sulfide (H2S)-releasing groups that can be coupled to existing pharmacologically active compounds.
Figure 2
Figure 2
Naturally occurring H2S-donating compounds.
Figure 3
Figure 3
The sulfur-containing amino acids.
Figure 4
Figure 4
The structures of selected thiol amino acids.
Figure 5
Figure 5
The structures of selected ACE inhibitors.
Figure 6
Figure 6
The structures of (A) Zofenopril and (B) Zofenoprilat. The asterisks denote the S configurations at the chiral centers. The arrow points to the only carbon atom whose configuration leads to R-Zofenoprilat.
Figure 7
Figure 7
The structure of Enalapril.
Figure 8
Figure 8
The structures of renin inhibitors Remikiren and Enalkiren.
Figure 9
Figure 9
The structures of selected endothelin receptor antagonists.
Figure 10
Figure 10
The structures of selected inhibitors of phosphodiesterase activity.
Figure 11
Figure 11
The structure of calcium-channel blocker (Diltiazem).
Figure 12
Figure 12
The structures of Sulpiride and Sultopride.
Figure 13
Figure 13
The structures of the H2S-releasing L-DOPA derivatives (ACS83, ACS84, ACS85, and ACS86).
Figure 14
Figure 14
The structures of selected HS-NSAIDs.
Figure 15
Figure 15
The structures of selective COX-2 inhibitors.
Figure 16
Figure 16
The structures of Propylthiouracil, Thiamazole and Carbimazole.
Figure 17
Figure 17
The structures of Thiamylal, Thiopental and Thiobarbital.
Figure 18
Figure 18
The structures of Cimetidine and Disulfiram.
Figure 19
Figure 19
The structures of selected androgen receptor (AR) antagonists.
See this image and copyright information in PMC

References

    1. Wang R. Physiological Implications of Hydrogen Sulfide: A Whiff Exploration That Blossomed. Physiol. Rev. 2012;92:791–896. doi: 10.1152/physrev.00017.2011. - DOI - PubMed
    1. Abe K., Kimura H. The possible role of hydrogen sulfide as an endogenous neuromodulator. J. Neurosci. 1996;16:1066–1071. doi: 10.1523/JNEUROSCI.16-03-01066.1996. - DOI - PMC - PubMed
    1. Kruszyna H., Kruszyna R., Smith R.P. Cyanide and sulfide interact with nitrogenous compounds to influence the relaxation of various smooth muscles. Proc. Soc. Exp. Biol. Med. 1985;179:44–49. doi: 10.3181/00379727-179-42062. - DOI - PubMed
    1. Kombian S.B., Warenycia M.W., Mele F.G., Reiffenstein R.J. Effects of acute intoxication with hydrogen sulfide on central amino acid transmitter systems. Neurotoxicology. 1988;9:587–595. - PubMed
    1. Warenycia M.W., Goodwin L.R., Benishin C.G., Reiffenstein R.J., Francom D.M., Taylor J.D., Dieken F.P. Acute hydrogen sulfide poisoning. Demonstration of selective uptake of sulfide by the brainstem by measurement of brain sulfide levels. Biochem. Pharm. 1989;38:973–981. doi: 10.1016/0006-2952(89)90288-8. - DOI - PubMed

Publication types

LinkOut - more resources